Online citations, reference lists, and bibliographies.
← Back to Search

Citrate--new Functions For An Old Metabolite.

V. Iacobazzi, V. Infantino
Published 2014 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Share
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
Citrate is an important substrate in cellular energy metabolism. It is produced in the mitochondria and used in the Krebs cycle or released into cytoplasm through a specific mitochondrial carrier, CIC. In the cytosol, citrate and its derivatives, acetyl-CoA and oxaloacetate, are used in normal and pathological processes. Beyond the classical role as metabolic regulator, recent studies have highlighted that citrate is involved in inflammation, cancer, insulin secretion, histone acetylation, neurological disorders, and non-alcoholic fatty liver disease. Monitoring changes in the citrate levels could therefore potentially be used as diagnostic tool. This review highlights these new aspects of citrate functions.
This paper references
10.1126/SCIENCE.123.3191.309
[Origin of cancer cells].
O. Warburg (1956)
Regulation of pyruvate dehydrogenase in muscle. Inhibition by citrate.
W. M. Taylor (1973)
10.1007/BF01558459
Correlation of the effects of citric acid cycle metabolites on succinate oxidation by rat liver mitochondria and submitochondrial particles
M. Hillar (1975)
Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells.
L. J. Reitzer (1979)
10.1016/S0005-2728(89)80160-4
Molecular aspects of isolated and reconstituted carrier proteins from animal mitochondria.
R. Kraemer (1989)
10.1016/S0005-2728(89)80068-4
Identification and purification of the tricarboxylate carrier from rat liver mitochondria.
F. Bisaccia (1989)
10.3109/10715769009148579
Superoxide-dependent formation of hydroxyl radicals from ferric-complexes and hydrogen peroxide: an evaluation of fourteen iron chelators.
J. Gutteridge (1990)
10.1016/0005-2728(90)90201-E
Kinetic characterization of the reconstituted tricarboxylate carrier from rat liver mitochondria.
F. Bisaccia (1990)
10.1016/0891-5849(92)90091-T
Ferritin as a source of iron for oxidative damage.
D. Reif (1992)
10.3109/10715769209068164
A chelator is required for microsomal lipid peroxidation following reductive ferritin-iron mobilisation.
J. G. Goddard (1992)
10.1016/s0021-9258(19)38701-0
The mitochondrial tricarboxylate transport protein. cDNA cloning, primary structure, and comparison with other mitochondrial transport proteins.
R. S. Kaplan (1993)
10.1007/BF01108409
Functional properties of purified and reconstituted mitochondrial metabolite carriers
F. Palmieri (1993)
10.1002/PROS.2990240307
Isocitric and citric acid in human prostatic and seminal fluid: Implications for prostatic metabolism and secretion
J. P. Kavanagh (1994)
10.1046/j.1471-4159.1994.62051727.x
Uptake, Release, and Metabolism of Citrate in Neurons and Astrocytes in Primary Cultures
N. Westergaard (1994)
10.1074/JBC.270.14.7864
CAAX Geranylgeranyl Transferase Transfers Farnesyl as Efficiently as Geranylgeranyl to RhoB (*)
S. A. Armstrong (1995)
10.1074/jbc.272.6.3324
Inhibition of Carnitine Palmitoyltransferase I Augments Sphingolipid Synthesis and Palmitate-induced Apoptosis*
M. Paumen (1997)
10.1002/(SICI)1097-0045(19990215)38:3<237::AID-PROS8>3.0.CO;2-O
Citrate in the diagnosis of prostate cancer
L. Costello (1999)
10.1148/RADIOLOGY.213.2.R99NV23473
Prostate cancer: localization with three-dimensional proton MR spectroscopic imaging--clinicopathologic study.
J. Scheidler (1999)
10.1128/MMBR.64.2.435-459.2000
Acetylation of Histones and Transcription-Related Factors
D. E. Sterner (2000)
10.1159/000012183
The Intermediary Metabolism of the Prostate: A Key to Understanding the Pathogenesis and Progression of Prostate Malignancy
L. Costello (2000)
10.1038/ng948
Mutant deoxynucleotide carrier is associated with congenital microcephaly
M. J. Rosenberg (2002)
10.1016/S1096-7192(03)00140-9
Screening of nine SLC25A13 mutations: their frequency in patients with citrin deficiency and high carrier rates in Asian populations.
Keiko Kobayashi (2003)
10.1038/nrm1075
Histone acetylation and deacetylation in yeast
S. Kurdistani (2003)
10.1002/ana.20282
Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation
C. Miller (2004)
10.1038/SJ.EMBOJ.7600062
Change and continuity
F. Gannon (2004)
10.1038/sj.emboj.7600244
Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
F. Yeung (2004)
10.1007/s00424-003-1099-7
The mitochondrial transporter family (SLC25): physiological and pathological implications
F. Palmieri (2004)
10.1038/sj.onc.1208773
ATP citrate lyase is an important component of cell growth and transformation
D. Bauer (2005)
10.1146/ANNUREV.BIOENG.7.060804.100411
In vivo magnetic resonance spectroscopy in cancer.
R. Gillies (2005)
10.1038/nature03985
A network-based analysis of systemic inflammation in humans
S. Calvano (2005)
10.1016/J.CCR.2005.06.015
Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer.
S. Lee (2005)
10.1259/BJR/11253478
MR imaging and MR spectroscopic imaging in the pre-treatment evaluation of prostate cancer.
H. Hricak (2005)
10.1016/J.CCR.2005.06.017
HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability.
J. Isaacs (2005)
10.1016/J.CCR.2005.04.005
Protein farnesylation: implications for normal physiology, malignant transformation, and cancer therapy.
S. Sebti (2005)
10.1152/AJPENDO.00218.2004
Perspective: emerging evidence for signaling roles of mitochondrial anaplerotic products in insulin secretion.
M. MacDonald (2005)
10.1101/GAD.1304105
Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins.
S. Willis (2005)
10.1186/1471-2091-7-10
EAAC1 is expressed in rat and human prostate epithelial cells; functions as a high-affinity L-aspartate transporter; and is regulated by prolactin and testosterone
R. Franklin (2006)
10.1002/mrm.20909
Quantitative analysis of prostate metabolites using 1H HR‐MAS spectroscopy
M. Swanson (2006)
10.1074/jbc.M602606200
The Mitochondrial Citrate/Isocitrate Carrier Plays a Regulatory Role in Glucose-stimulated Insulin Secretion*
J. Joseph (2006)
10.1016/J.JURO.2006.07.054
Citrate concentrations in human seminal fluid and expressed prostatic fluid determined via 1H nuclear magnetic resonance spectroscopy outperform prostate specific antigen in prostate cancer detection.
E. Kline (2006)
10.1016/J.CMET.2006.02.002
HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia.
J. Kim (2006)
10.1097/01.mco.0000241661.15514.fb
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase and tumor cell glycolysis
J. Chesney (2006)
10.1186/1476-4598-5-17
The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots
L. Costello (2006)
10.1073/pnas.0704652104
Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer
L. Shen (2007)
10.1101/GAD.1529107
The transcription factor HIF-1alpha plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis.
J. Lum (2007)
10.1016/J.BBRC.2007.02.114
Transcription of the mitochondrial citrate carrier gene: role of SREBP-1, upregulation by insulin and downregulation by PUFA.
V. Infantino (2007)
10.1093/HMG/DDM275
Succinate inhibition of α-ketoglutarate-dependent enzymes in a yeast model of paraganglioma
E. H. Smith (2007)
10.1016/j.cell.2007.01.015
The Role of Chromatin during Transcription
Bing Li (2007)
10.1152/ajpendo.90604.2008
Metabolic cycling in control of glucose-stimulated insulin secretion.
M. Jensen (2008)
10.2174/156652408783769580
Unique biology of Mcl-1: therapeutic opportunities in cancer.
M. Warr (2008)
10.1016/j.ajhg.2008.09.009
Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal mitochondrial disease.
C. Sugiana (2008)
10.1016/j.bbrc.2008.08.015
Epigenetic mechanisms and Sp1 regulate mitochondrial citrate carrier gene expression.
V. Iacobazzi (2008)
10.1126/science.1164097
ATP-Citrate Lyase Links Cellular Metabolism to Histone Acetylation
K. Wellen (2009)
10.1016/j.bbrc.2009.06.003
Transcription of the mitochondrial citrate carrier gene: identification of a silencer and its binding protein ZNF224.
V. Iacobazzi (2009)
10.1074/jbc.M109.016816
Nuclear Targeting of 6-Phosphofructo-2-kinase (PFKFB3) Increases Proliferation via Cyclin-dependent Kinases*
A. Yalcin (2009)
10.1056/NEJMoa0900591
AGC1 deficiency associated with global cerebral hypomyelination.
R. Wibom (2009)
10.1016/j.bbrc.2009.05.030
Role of FOXA in mitochondrial citrate carrier gene expression and insulin secretion.
V. Iacobazzi (2009)
10.1093/hmg/ddp370
A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity.
P. Morciano (2009)
10.1038/nature08617
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
L. Dang (2009)
10.1016/j.yexmp.2009.01.003
Regulation of glucose metabolism by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases in cancer.
A. Yalcin (2009)
Effect of citrate on malignant pleural mesothelioma cells: a synergistic effect with cisplatin.
Xiaodong Zhang (2009)
10.1016/j.molcel.2010.06.022
Activation of a metabolic gene regulatory network downstream of mTOR complex 1.
K. Düvel (2010)
10.1038/embor.2010.51
Molecular origin of plasma membrane citrate transporter in human prostate epithelial cells
Maciej P. Mazurek (2010)
10.1016/j.ccr.2010.11.015
Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation.
M. Figueroa (2010)
10.1007/s13277-010-0125-6
Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate
D. Rakheja (2011)
10.1074/jbc.M109.097188
Identification and Functional Characterization of a Novel Mitochondrial Carrier for Citrate and Oxoglutarate in Saccharomyces cerevisiae*
Alessandra Castegna (2010)
10.1038/onc.2009.358
Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer
R. DeBerardinis (2010)
10.1016/j.ccr.2010.12.014
Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases.
W. Xu (2011)
10.1016/j.bbrc.2011.07.047
Identification of a novel Sp1 splice variant as a strong transcriptional activator.
V. Infantino (2011)
10.1042/BJ20111386
A critical role for citrate metabolism in LPS signalling.
L. O'Neill (2011)
Citrate induces apoptotic cell death: a promising way to treat gastric carcinoma?
Y. Lu (2011)
10.1038/nrd3504
Targeting cancer metabolism: a therapeutic window opens
M. V. Heiden (2011)
10.1016/j.molmed.2011.06.001
Revisiting the TCA cycle: signaling to tumor formation.
N. Raimundo (2011)
10.1042/BJ20111275
The mitochondrial citrate carrier: a new player in inflammation.
V. Infantino (2011)
10.1038/embor.2011.43
The oncometabolite 2‐hydroxyglutarate inhibits histone lysine demethylases
R. Chowdhury (2011)
10.1186/1476-4598-10-70
The metabolic advantage of tumor cells
M. Israël (2011)
10.1073/pnas.1117773108
Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability
D. Wise (2011)
10.1002/ajmg.a.34344
Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency
Amelia R Mroch (2012)
10.1210/en.2011-1562
The mitochondrial citrate carrier (CIC) is present and regulates insulin secretion by human male gamete.
A. Cappello (2012)
10.1038/nature10602
Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
C. Metallo (2011)
10.1016/j.biocel.2012.01.003
Citrate carrier promoter is target of peroxisome proliferator-activated receptor alpha and gamma in hepatocytes and adipocytes.
F. Damiano (2012)
10.1016/j.ccr.2012.02.014
Metabolic reprogramming: a cancer hallmark even warburg did not anticipate.
Patrick S Ward (2012)
10.1074/jbc.M112.362343
NAD+-dependent Sirtuin 1 and 6 Proteins Coordinate a Switch from Glucose to Fatty Acid Oxidation during the Acute Inflammatory Response*
T. Liu (2012)
10.1016/j.bbrc.2012.06.002
IDH1 and IDH2 have critical roles in 2-hydroxyglutarate production in D-2-hydroxyglutarate dehydrogenase depleted cells.
H. Matsunaga (2012)
10.1007/s00018-012-1166-3
Citrate kills tumor cells through activation of apical caspases
Björn Kruspig (2012)
10.18632/ONCOTARGET.714
The mitochondrial citrate transporter, CIC, is essential for mitochondrial homeostasis
Olga Catalina-Rodriguez (2012)
10.1016/j.cmet.2011.12.009
Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells.
A. Le (2012)
10.1038/ni.2550
Microtubule-driven spatial arrangement of mitochondria promotes activation of the NLRP3 inflammasome
T. Misawa (2013)
10.1038/nature11986
Succinate is an inflammatory signal that induces IL-1β through HIF-1α
G. Tannahill (2013)
10.1136/jmedgenet-2012-101485
Agenesis of corpus callosum and optic nerve hypoplasia due to mutations in SLC25A1 encoding the mitochondrial citrate transporter
S. Edvardson (2013)
10.1016/j.euroneuro.2012.08.015
Insight into mechanism of in vitro insulin secretion increase induced by antipsychotic clozapine: Role of FOXA1 and mitochondrial citrate carrier
A. Menga (2013)
10.1016/j.bbrc.2013.09.037
ATP-citrate lyase is essential for macrophage inflammatory response.
V. Infantino (2013)
10.1038/nature11862
Metabolism of inflammation limited by AMPK and pseudo-starvation
L. O’Neill (2013)
10.1016/j.bbalip.2013.01.014
Mechanisms of divergent effects of activated peroxisome proliferator-activated receptor-γ on mitochondrial citrate carrier expression in 3T3-L1 fibroblasts and mature adipocytes.
D. Bonofiglio (2013)
10.1016/j.mam.2012.05.005
The mitochondrial transporter family SLC25: identification, properties and physiopathology.
F. Palmieri (2013)
10.1074/jbc.R113.486464
How Metabolism Generates Signals during Innate Immunity and Inflammation*
A. F. mcGettrick (2013)
10.1016/j.febslet.2013.06.019
Elevated citrate levels in non‐alcoholic fatty liver disease: The potential of citrate to promote radical production
B. van de Wier (2013)
10.1016/j.ajhg.2013.03.009
Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.
B. Nota (2013)



This paper is referenced by
10.1016/j.fertnstert.2021.02.031
Adenomyosis is associated with specific proton nuclear magnetic resonance (1H-NMR) serum metabolic profiles.
M. Bourdon (2021)
10.1002/advs.202101553
Citrate Promotes Excessive Lipid Biosynthesis and Senescence in Tumor Cells for Tumor Therapy.
Yangjing Zhao (2021)
10.3389/fmicb.2021.673881
Molecular Mechanism of Citrate Efflux by the Mitochondrial Citrate Transporter CT in Filamentous Fungus Mucor circinelloides WJ11
Wu Yang (2021)
10.1007/s11010-021-04281-4
Active mitochondrial respiration in cancer: a target for the drug.
Minakshi Bedi (2021)
10.1016/B978-0-12-822467-0.00008-5
Sirtuins and cellular metabolism in cancers
Z. Dong (2021)
10.1101/2021.10.24.21265434
Plasma metabolomics profiling and machining learning-driven prediction of nonalcoholic steatohepatitis
M. Ji (2021)
10.1159/000515434
Gene Transfer Therapy for Neurodevelopmental Disorders
C. Ozlu (2021)
10.1007/s00204-021-02974-9
Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis.
Amin Gasmi (2021)
10.1016/j.plabm.2021.e00213
High-throughput nuclear magnetic resonance measurement of citrate in serum and plasma in the clinical laboratory
Erwin Garcia (2021)
10.1016/j.canlet.2020.12.020
Metabolic adaptation in hypoxia and cancer.
F. Paredes (2021)
10.7554/eLife.62394
ACLY ubiquitination by CUL3-KLHL25 induces the reprogramming of fatty acid metabolism to facilitate iTreg differentiation
Miaomiao Tian (2021)
10.1016/j.ejphar.2021.174490
Candidates for smart cardiovascular medical device coatings: A comparative study with endothelial and smooth muscle cells.
Miriama Ceresnakova (2021)
10.1177/00220345211051594
METTL3-Dependent Glycolysis Regulates Dental Pulp Stem Cell Differentiation.
(2021)
10.1016/J.EURPOLYMJ.2021.110271
Citric acid: A green cross-linker of biomaterials for biomedical applications
R. Salihu (2021)
10.1038/s41467-021-23545-7
Restoration of energy homeostasis by SIRT6 extends healthy lifespan
A. Roichman (2021)
10.3390/life11010069
Tricarboxylic Acid (TCA) Cycle Intermediates: Regulators of Immune Responses
Inseo Choi (2021)
10.3389/fcell.2021.626316
Warburg’s Ghost—Cancer’s Self-Sustaining Phenotype: The Aberrant Carbon Flux in Cholesterol-Enriched Tumor Mitochondria via Deregulated Cholesterogenesis
P. Coleman (2021)
10.4239/wjd.v12.i8.1164
Current progress in metabolomics of gestational diabetes mellitus
Qian-Yi Wang (2021)
ATVB IN FOCUS: Trained Immunity and Vascular Disease
Charles Drummer (2021)
10.3390/ijms22126587
Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update
P. Icard (2021)
10.3390/metabo11100706
Molecular Mechanisms of the SLC13A5 Gene Transcription
Zhihui Li (2021)
10.3390/cells10112962
ACLY Nuclear Translocation in Human Macrophages Drives Proinflammatory Gene Expression by NF-κB Acetylation
(2021)
10.1093/bioinformatics/btab177
Queueing theory model of Krebs cycle
Sylwester Kloska (2021)
10.1111/acel.13510
Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis.
Shou-Zen Fan (2021)
10.1038/s41581-021-00413-7
Targeting immune cell metabolism in kidney diseases
P. J. Basso (2021)
10.1038/s41598-021-90644-2
Childhood overeating is associated with adverse cardiometabolic and inflammatory profiles in adolescence
Christopher Hübel (2021)
10.1177/15353702211009228
Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors
(2021)
10.1371/journal.pgen.1008884
The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP
F. Szeri (2020)
10.3390/biom10091242
Hormone-Independent Mouse Mammary Adenocarcinomas with Different Metastatic Potential Exhibit Different Metabolic Signatures
Daniela Bispo (2020)
10.3390/insects11120851
Comparative Fecal Metabolomes of Silkworms Being Fed Mulberry Leaf and Artificial Diet
D. Qin (2020)
10.1021/acscentsci.0c00518
High-Performance Intensiometric Direct- and Inverse-Response Genetically Encoded Biosensors for Citrate
Yufeng Zhao (2020)
10.1101/2020.11.22.393413
Operation of a TCA cycle subnetwork in the mammalian nucleus
Eleni Kafkia (2020)
See more
Semantic Scholar Logo Some data provided by SemanticScholar